| 兰凯 张光伟 常远武晓慧.骨化三醇干预糖尿病肾病大鼠蛋白尿发生机制的研究[J].,2015,15(31):6035-6038 |
| 骨化三醇干预糖尿病肾病大鼠蛋白尿发生机制的研究 |
| Mechanismof Proteinuria Prevention by 1,25- (OH)2D3 in DiabeticNephropathy Rats |
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| DOI： |
| 中文关键词: 糖尿病肾病 蛋白尿 骨化三醇 |
| 英文关键词: Diabetic nephropathy Proteinuria Calcitrol |
| 基金项目:陕西省教育厅科技基金计划项目（14JK1625） |
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| 中文摘要: |
| 目的：观察骨化三醇对糖尿病肾病（diabetic nephropathy，DN）大鼠肾组织中肾素水平，肾小球基底膜乙酰肝素酶（Heparanases，
HPA）和足细胞podocin 蛋白及mRNA 表达的影响，并探讨其可能机制。方法：采用链尿佐菌素(streptozotocin，STZ)腹腔注射的方
法构建DN大鼠动物模型，将造模成功的大鼠随机分为骨化三醇组（T组）、DN 组（D 组），并设置健康对照组（N 组）。T 组给予
0.03 滋g·kg-1·d-1的骨化三醇灌胃；D组与N组给予等量花生油灌胃。12 周后检测24小时尿蛋白定量及血生化指标，通过ELISA
法检测肾组织中肾素和血管紧张素Ⅱ（angiotensinⅡ，AngⅡ）浓度变化，免疫组化法和RT-PCR检测HPA、podocin 蛋白及mRNA
的表达。结果：与N 组相比，T 组和D 组24 小时尿蛋白定量、血清肌酐、肾素及AngⅡ水平较高，D 组显著高于T组，差异均有统
计学意义（P<0.05）。与N组相比，T 组和D 组HPA mRNA及蛋白表达较高，D 组显著高于T组；T 组和D 组podocin mRNA 及
蛋白表达较低，D 组显著低于T 组，差异均有统计学意义（P<0.05）。肾素和HPA 蛋白表达存在正相关趋势（r=0.79，P<0.05）；和
podocin 蛋白表达存在负相关趋势（r=-0.65 ，P<0.05）。结论：骨化三醇可显著减少DN 大鼠早期蛋白尿，此作用可能通过抑制肾素，
下调DN肾小球基底膜HPA、上调足细胞podocin 蛋白的表达实现。 |
| 英文摘要: |
| Objective:To study the effects of calcitrol on the level of renin, the expression of heparanases (HPA) and podocin protein
in the kidney of diabetic nephropathy (DN) rats and its possible mechanism.Methods:DN model rats were established by intraperitoneal
injection with streptozotocin（STZ）. All the DN rats were randomly divided into calcitrol group(group T) and DN group (group D).
Healthy rats were chosen as healthy control group(group N).Group T were treated with 0.03 ug·kg-1·d-1 of calcitrol gavage. Group D and
group N were given equal amount of peanut oil gavage. 24 h urinary protein and serum biochemical indicators were examined after 12
weeks. ELISA methods were applied to detect the concentration change of renin and AngⅡ in the kidney, Immunohistochemistry and
RT-PCR methods were applied to detect the protein and mRNA expression of HPA and podocin.Results:Compared with group N, 24 h
urinary protein, serum creatinine, renin and AngⅡ of T group and D group were markedly increased, and they were significantly higher
in group D than that in groupT (P<0.05). Compared with group N, the expression of HPA mRNA and protein in group T and group D
was markedly increased, and higher expression was found in group D (P<0.05). The expression of podocin mRNA and protein in group T
and group D was markedly decreased, and they were significantly lower in group D (P<0.05). There was direct correlation between renin
and HPA expression (r=0.79 P<0.05), and inverse correlation between renin and podocin protein expression (r=-0.65 P<0.05).Conclusion:Calcitrol can significantly reduce the proteinuria, which may be associated with inhibiting the renin by down-regulate protein expression
of HPA of glomerular basement membrane and up-regulate the protein expression of podocin of podocyte. |
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